title: Antimalarial activity of compounds comprising a primary benzene sulfonamide fragment.
abstract: Despite the urgent need for effective antimalarial drugs with novel modes of action no new chemical class of antimalarial drug has been approved for use since 1996. To address this, we have used a rational approach to investigate compounds comprising the primary benzene sulfonamide fragment as a potential new antimalarial chemotype. We report the in vitro activity against Plasmodium falciparum drug sensitive (3D7) and resistant (Dd2) parasites for a panel of fourteen primary benzene sulfonamide compounds. Our findings provide a platform to support the further evaluation of primary benzene sulfonamides as a new antimalarial chemotype, including the identification of the target of these compounds in the parasite.
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111, Australia; Queensland Institute of Medical Research, Herston, Queensland 4029, Australia. Electronic address: Kathy.Andrews@qimr.edu.au.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Andrews
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Fisher
authors.forename: Subathdrage D M
authors.initials: SD
authors.lastname: Sumanadasa
authors.forename: Tina
authors.initials: T
authors.lastname: Skinner-Adams
authors.forename: Janina
authors.initials: J
authors.lastname: Moeker
authors.forename: Marie
authors.initials: M
authors.lastname: Lopez
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Poulsen
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000737:chemistry* / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D001555:Benzene Derivatives; D013449:Sulfonamides
keywords: Antimalarial; Carbonic anhydrase; NFF; Plasmodium falciparum; Primary sulfonamide; Ro5; SAR; SPR; Structure–activity relationships; Structure–property relationships; Sulfonamide; neonatal foreskin fibroblast; rule of 5 violations